Subcutaneous Immunization of Dogs With Bordetella bronchiseptica Bacterial Ghost Vaccine

Abstract

The Bordetella species are Gram-negative bacterial pathogens that colonizes mammalian respiratory tract causing respiratory diseases in humans and animals. B. bronchiseptica causes clinical conditions in many mammals including immunocompromised humans. Using the dog model of respiratory infection, it has been shown in this study that a newly developed B. bronchiseptica Bacterial Ghost (BbBG) vaccine exhibited significant protection in the face of a severe pathogenic bacterial challenge in seronegative dogs. The protein E -specific lysis mechanism was used to produce BbBGs. Bacterial Ghosts (BGs) are the empty cell envelope of Gram-negative bacterium. They are genetically processed to form a microscopic hole in their membrane, through which all the cytoplasmic contents are expelled leaving behind intact empty bacterial shells. Due to the intact surface structures of BGs, they offer the safety of inactivated but efficacy of live attenuated vaccines. In this study, seronegative dogs were vaccinated subcutaneously (s/c) with two different doses of a newly developed BbBG vaccine [lower 10 ∧ 5 (BbBG – 5) and higher 10 ∧ 7 (BbBG – 7)] on day 0 and 21. The animals were challenged (by aerosol) with virulent live B. bronchiseptica strains 41 days after first vaccination. The dogs vaccinated s/c with BbBG – 7 vaccine had significantly lower spontaneous coughing scores ( P = 0.0001) than dogs in negative control group. Furthermore, the tested BbBG – 7 vaccine was equivalent to the positive control vaccine Bronchicine CAe in terms of safety and efficacy. For the first time, we report the successful use of liquid formulated BGs vaccines in animal studies. Earlier reported studies using BGs vaccines were performed with resuspended freeze-dried BGs preparations.

Bacterial Ghosts-Based Vaccine and Drug Delivery Systems

“…Currently, regulation of the expression of the gene E lysis system has been successfully applied against several gram-negative bacteria strains, Salmonella typhimurium [37], Salmonella enteritidis [8], Vibrio cholerae [38], Pectobacterium cypripedii [39], Helicobacter pylori [40], Actinobacillus-pleuropneumoniae [41], Haemophilus influenzae [42], Pasteurella multocida [43], Brucella [44], and Aeromonas hydrophila [45], among others. Given the wide spectrum of bacteria, these findings imply that any suitable gene E carrier, perhaps all Gram-negative bacteria, can produce lysis-based BGs.…”

Comparative Proteomic Analysis Reveals Complex Responses to Bordetella bronchiseptica Infections in the Spleen of Rabbits

“…[ 23 ] B. bronchiseptica results in pulmonary fibrosis and impetigo. [ 9 ] However, the basis of these effects is unknown given the lack of knowledge of the protein profile of the B. bronchiseptica ‐infected rabbit spleen cells. TMT labeling and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) have revealed DAPs in spleen cells of rabbits infected with B. bronchiseptica and may supply the possibility to get the knowledge of the protein profile of the B. bronchiseptica ‐infected rabbit spleen cells.…”

“…[ 4–7 ] By contrast, it is a very common pathogen in animals, and infects the respiratory tract of some mammals. [ 1,8 ] B. bronchiseptica is related to infectious respiratory disease complex in canines [ 9 ] and infection of the respiratory system causes a common and deadly disease in rabbits. B. bronchiseptica infection occurs throughout the year, more commonly in the spring and autumn.…”

A Novel and Efficient High-Yield Method for Preparing Bacterial Ghosts

“…Up to now, numerous bacteria besides the model strain E. coli have been successfully used to produce BGs, for example, Salmonella enteritidis [21], Vibrio parahaemolyticus [22], Pasteurella multocida [23], and Bordetella bronchiseptica [24]. Salmonella enterica serovar Enteritidis (S. enterica, SE) is a facultative anaerobic Gram-negative bacterium which frequently causes diarrhea and systemic infections of human and animals [25].…”